Proliferation of microvascular endothelium is an important event in the growth of malignant solid tumors but the mechanism(s) underlying this response are not completely understood. The present study is being undertaken to gain further insight into the mechanism(s) of tumor neovascularization by examining the potential regulatory role of tumor infiltrates, particularly monocytes and macrophages, in the initiation and/or maintenance of neovascular responses induced by tumors and to determine the significance of such an interrelationship in the control of tumor growth. Studies will entail: 1) a kinetic study of 3H-thymidine (3H-T) incorporation by endothelial cells at various stages in the malignant progression of epithelial tumors induced by 9-10 dimethyl, 1-2 benzanthracine in the hamster cheek pouch, 2) a correlation of the onset and magnitude of endothelial 3H-T labeling with the distribution and extent of monocyte/macrophage infiltration at sites of tumor development, 3) an autoradiographic analysis of the angiogenic response to tumors in hamsters depleted of monocytes and macrophages by treatment with antimacrophage serum hydrocortisone acetate, and 4) an examination of the angiogenic potential of these and other tumor derived leukocytes following the introduction of cells and conditioned media into the avascular cornea of the guinea pig eye.